De Angelis Federico, Breccia Massimo
Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161 Rome, Italy.
Rare Cancers Ther. 2015;3(1):119-132. doi: 10.1007/s40487-015-0013-8. Epub 2015 Oct 21.
Acute promyelocytic leukemia (APL) is a molecularly well-defined disease, characterized by a specific chromosomal translocation; the improvement in biologic and clinical knowledge and subsequent introduction of molecularly targeted therapies have transformed the management of APL, with survival rates now exceeding 80%. Minimal residual disease (MRD) assessment in APL is the most important tool for its treatment; the prognostic role of the molecular detection of promyelocytic leukemia retinoic acid receptor α (PML-RARα) transcript after consolidation therapy in the early identification of the following hematologic relapse is now well established and guides preemptive therapy. First experiences performed with a qualitative polymerase chain reaction (PCR) approach were replaced with more accurate real-time quantitative PCR (RQ-PCR), which guarantees a numeric quantification of MRD. The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARα with innovative therapy different from the standard ones. MRD monitoring demonstrated its validity also in the setting of relapsed patients with interesting results in the autologous and allogeneic stem cell transplantation setting or with the use of other biological agents. The aim of this review is to report and discuss the actual state of the art of MRD in APL.
急性早幼粒细胞白血病(APL)是一种分子特征明确的疾病,其特征为特定的染色体易位;生物学和临床知识的进步以及随后分子靶向疗法的引入改变了APL的治疗方式,目前生存率已超过80%。APL中的微小残留病(MRD)评估是其治疗的最重要工具;巩固治疗后早幼粒细胞白血病视黄酸受体α(PML-RARα)转录本的分子检测在早期识别后续血液学复发中的预后作用现已得到充分证实,并指导抢先治疗。最初采用定性聚合酶链反应(PCR)方法的经验已被更准确的实时定量PCR(RQ-PCR)所取代,后者可保证对MRD进行数值定量。三氧化二砷(ATO)不仅被证实是复发患者的有效治疗方法,而且可作为单独标准治疗或与全反式维甲酸联合使用的替代方案,考虑到与标准疗法不同的创新疗法可能对PML-RARα有不同的清除效果,这扩大了APL患者MRD评估的验证范围。MRD监测在复发患者中也证明了其有效性,在自体和异基因干细胞移植环境中或使用其他生物制剂时均取得了有趣的结果。本综述的目的是报告和讨论APL中MRD的当前技术水平。